Development and validation of a random survival forest model for predicting long-term survival of early-stage young breast cancer patients based on the SEER database and an external validation cohort.

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

Safety and oncological outcome of early intraoperative intravesicle mitomycin C vs. deferred instillation in patients receiving robot-assisted radical nephroureterectomy.

Introduction: Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. Methods: This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. Results: A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. Conclusion: IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

Structural and functional insights into transcription activation of the essential LysR-type transcriptional regulators.

The enormous LysR-type transcriptional regulators (LTTRs), which are diversely distributed amongst prokaryotes, play crucial roles in transcription regulation of genes involved in basic metabolic pathways, virulence and stress resistance. However, the precise transcription activation mechanism of these genes by LTTRs remains to be explored. Here, we determine the cryo-EM structure of a LTTR-dependent transcription activation complex comprising of Escherichia coli RNA polymerase (RNAP), an essential LTTR protein GcvA and its cognate promoter DNA. Structural analysis shows two N-terminal DNA binding domains of GcvA (GcvA_DBD) dimerize and engage the GcvA activation binding sites, presenting the -35 element for specific recognition with the conserved σ70R4. In particular, the versatile C-terminal domain of α subunit of RNAP directly interconnects with GcvA_DBD, σ70R4 and promoter DNA, providing more interfaces for stabilizing the complex. Moreover, molecular docking supports glycine as one potential inducer of GcvA, and single molecule photobleaching experiments kinetically visualize the occurrence of tetrameric GcvA-engaged transcription activation complex as suggested for the other LTTR homologs. Thus, a general model for tetrameric LTTR-dependent transcription activation is proposed. These findings will provide new structural and functional insights into transcription activation of the essential LTTRs.

A Deep Learning Approach to Classify Fabry Cardiomyopathy from Hypertrophic Cardiomyopathy Using Cine Imaging on Cardiac Magnetic Resonance.

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

Color stability of CAD-CAM hybrid ceramic materials following immersion in artificial saliva and wine.

PURPOSE: To examine the color stability of 3D-printed and milled, interim, and definitive, restorative materials after immersion in artificial saliva and wine for 1, 3, and 6 months. MATERIAL AND METHODS: The study used a 2 × 5 factorial design with 10 subgroups, including 2 immersion liquids (artificial saliva and wine) and 5 manufacturing technology and restorative material combinations (n = 10). Color measurements were taken using a contact-type digital spectrophotometer (CM-2600d Spectrophotometer; Konica Minolta Healthcare Americas Inc) before immersion and at 1 month (T1), 3 months (T3), and 6 months (T6) after immersion. The CIE2000 system was used to calculate quantitative measurements of color differences in ΔE00, and comparisons were made to the acceptability threshold (AT) and perceptibility threshold (PT). Repeated measures of ANOVA (α = 0.05) were used to compare differences in color changes between manufacturing technology/restorative material-immersion liquid combinations at T1, T3, and T6. RESULTS: To compare the effect of immersion liquid and time on the manufacturing technology/restorative material groups, the ΔE00 values were compared to the PT of 0.8 and the AT of 1.8. Wine caused significant color changes in ΔE00 values beyond the PT and AT values in all groups at all time intervals, except for the AT value of milled definitive crowns (hybrid nano-ceramic material). Wine immersion caused significant ΔE00 for all manufacturing technology/restorative material groups at all time intervals (1 month, 3 months, and 6 months) when compared to artificial saliva immersion (all p < 0.001). CONCLUSION: Upon exposure to artificial saliva, 80%-100% of samples from all groups remained within the acceptable and perceptible color change thresholds. The wine had significant chromogenic effects on all tested restorative materials, however, the milled definitive crowns (hybrid nano-ceramic material) showed the greatest color stability. For patients with heavy wine consumption, 3D-printed definitive crowns (hybrid ceramic-filled material) may show discoloration exceeding acceptable and perceptible color change limits.

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion.

INTRODUCTION: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. METHODS: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. RESULTS: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. CONCLUSIONS: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.

Tennis shot side-view and top-view data set for player analysis in Tennist.

Tennis is a popular sport, and the introduction of technology has allowed players to diversify their training. Tennis ball tracking is currently a focal point, serving not only to assist referees but also to enhance sports analysis. We introduce the Tennis Shot Side-View and Top-View Dataset, which serves as an invaluable resource for analyzing tennis movements and verifying landing positions after flight. This dataset combines side-view and top-view video clips, capturing various shot types and player movements from both outdoor and indoor fields. The dataset includes the actual ball positions of each clip for verification purposes. The Tennis Shot Side-View and Top-View Dataset represents a significant advancement in tennis research. Its multidimensional nature opens doors for in-depth player analysis, performance enhancement, and strategy development. We believe that this dataset will be a valuable asset to the tennis community, fostering innovation and excellence in the sport.

Arbuscular mycorrhizal fungi reduce soil N2O emissions by altering root traits and soil denitrifier community composition.

Arbuscular mycorrhizal fungi (AMF) increase the ability of plants to obtain nitrogen (N) from the soil, and thus can affect emissions of nitrous oxide (N2O), a long-lived potent greenhouse gas. However, the mechanisms underlying the effects of AMF on N2O emissions are still poorly understood, particularly in agroecosystems with different forms of N fertilizer inputs. Utilizing a mesocosm experiment in field, we examined the effects of AMF on N2O emissions via their influence on maize root traits and denitrifying microorganisms under ammonia and nitrate fertilizer input using 15N isotope tracer. Here we show that the presence of AMF alone or both maize roots and AMF increased maize biomass and their 15N uptake, root length, root surface area, and root volume, but led to a reduction in N2O emissions under both N input forms. Random forest model showed that root length and surface area were the most important predictors of N2O emissions. Additionally, the presence of AMF reduced the (nirK + nirS)/nosZ ratio by increasing the relative abundance of nirS-Bradyrhizobium and Rubrivivax with ammonia input, but reducing nosZ-Azospirillum, Cupriavidus and Rhodopseudomonas under both fertilizer input. Further, N2O emissions were significantly and positively correlated with the nosZ-type Azospirillum, Cupriavidus and Rhodopseudomonas, but negatively correlated with the nirS-type Bradyrhizobium and Rubrivivax. These results indicate that AMF reduce N2O emissions by increasing root length to explore N nutrients and altering the community composition of denitrifiers, suggesting that effective management of N fertilizer forms interacting with the rhizosphere microbiome may help mitigate N2O emissions under future N input scenarios.

Cross-cultural translation and validation of the Chinese version Distress Tolerance Scale for adolescents with chronic physical disease.

INTRODUCTION: Chronic physical disease (CPD) makes life filled with many negative events in adolescents, but not all adolescents experiencing negative life events proceed to develop emotional distress, only those with low emotional distress tolerance (EDT). A valid and reliable scale to measure EDT in CPD adolescents is important for caring for their emotional distress. Therefore, the purpose of this study is to translate the 15-item English version Distress Tolerance Scale (DTS) into a Chinese version and then validate the scale for measuring EDT of adolescents with CPD. METHODS: The 15-item English version DTS was translated into a Chinese version using the translation guidelines for cross-cultural research. Two cohorts of adolescents with CPD were recruited from four hospitals in southern Taiwan, with the first cohort including 124 adolescents with CPD employed to conduct exploratory factor analysis, corrected item-total correlation and reliability testing, while the second cohort, consisting of 238 adolescents with CPD, was utilized to examine confirmatory factor analysis and concurrent validity. RESULTS: The two-factor nine-item Chinese version DTS for Adolescents with CPD (C-DTS-A) was developed. Lower scores of the C-DTS-A were significantly associated with higher diabetes distress, poorer self-management, and worse glycaemic control; their correlation coefficients sequentially were -.40, .17 and -.23. Cronbach's α and the test-retest reliability of the two-factor C-DTS-A ranged from .81 to .87 and from .79 to .89, respectively. CONCLUSION: The two-factor nine-item C-DTS-A with good cross-cultural translation quality was a reliable and valid scale to assess EDT for adolescents with CPD.

The impact of base design and restoration type on the resin consumption, trueness, and dimensional stability of dental casts additively manufactured from liquid crystal display 3D printers.

PURPOSE: To evaluate the effects of two base types and three restoration designs on the resin consumption and trueness of the 3D-printed dental casts. Additionally, the study explored the dimensional stability of these 3D-printed dental casts after 1 year of storage. MATERIALS AND METHODS: Various types of reference dental casts were specifically designed to represent three types of dental restoration fabrications, including full-arch (FA), long-span (LS), and single-unit (SU) prostheses. The reference casts were digitized with a dental laboratory scanner and used to create flat and hollow base designs (N = 18) for the 3D-printed study casts. The 3D-printed study casts were digitized and evaluated against their corresponding references immediately after 3D printing and again after 1 year of storage, with the trueness quantified using the root mean square error (RMSE) at both time points. Volumes of resin used were recorded to measure resin consumption, and the weights of the 3D-printed study casts were also measured. The data were analyzed using two-way ANOVA and a Tukey post hoc test, α = 0.05. RESULTS: Volumetric analysis showed the flat-base design had significantly higher resin consumption with weights for the FA group at 42.51 ± 0.16 g, the LS group at 31.64 ± 0.07 g, and the SU group at 27.67 ± 0.31 g, as opposed to 26.22 ± 1.01 g, 22.86 ± 0.93 g, and 20.10 ± 0.19 g for the hollow designs respectively (p < 0.001). Trueness, assessed through two-way ANOVA, revealed that the flat-base design had lower RMSE values indicating better trueness in the LS (54 ± 6 µm) and SU (59 ± 7 µm) groups compared to the hollow-base design (LS: 73 ± 5, SU: 99 ± 11 µm, both p < 0.001), with no significant difference in the FA group (flat-base: 50 ± 3, hollow: 47 ± 5 µm, p = 0.398). After 1 year, the flat-base design demonstrated superior dimensional stability in the LS (flat base: 56 ± 6 µm, hollow base: 149 ±45 µm, p < 0.001) and SU groups (flat base: 95 ± 8 µm, hollow base: 183 ±27 µm, p < 0.001), with the FA group showing no significant difference in the base design (flat base: 47 ± 9, hollow base: 62 ± 12 µm, p = 0.428). CONCLUSIONS: The hollow-base design group showed lower resin consumption than the flat-base design group. However, the flat-base designs exhibited superior trueness and less distortion after 1 year of storage. These findings indicate that despite the higher material usage, flat-base designs provide better initial accuracy and maintain their dimensional stability over time for most groups.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

The tether function of the anoctamins.

The core functions of the anoctamins are Cl- channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.

Berberine alleviates diabetic retinopathy by regulating the Th17/Treg ratio.

BACKGROUND: Diabetic retinopathy (DR) stands as a prominent complication of diabetes. Berberine (BBR) has reported to be effective to ameliorate the retinal damage of DR. Studying the potential immunological mechanisms of BBR on the streptozotocin (STZ) induced DR mouse model will explain the therapeutic mechanisms of BBR and provide theoretical basis for the clinical application of this drug. METHODS: C57BL/6J mice were induced into a diabetic state using a 50 mg/(kg·d) dose of STZ over a 5-day period. Subsequently, they were subjected to a high-fat diet (HFD) for one month. Following a 5-week treatment with 100 mg/(kg·d) BBR, the concentrations of inflammatory factors in the mice's peripheral blood were determined using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin staining was employed to scrutinize pathological changes in the mice's retinas, while flow cytometry assessed the proportions of T-lymphocyte subsets and the activation status of dendritic cells (DCs) in the spleen and lymph nodes. CD4+T cells and DC2.4 cell lines were utilized to investigate the direct and indirect effects of BBR on T cells under high glucose conditions in vitro. RESULTS: Following 5 weeks of BBR treatment in the streptozotocin (STZ) mouse model of DR, we observed alleviation of retinal lesions and a down-regulation in the secretion of inflammatory cytokines, namely TNF-α, IL-1ß, and IL-6, in the serum of these mice. And in the spleen and lymph nodes of these mice, BBR inhibited the proportion of Th17 cells and promoted the proportion of Treg cells, thereby down-regulating the Th17/Treg ratio. Additionally, in vitro experiments, BBR directly inhibited the expression of the transcription factor RORγt and promoted the expression of the transcription factor Foxp3 in T cells, resulting in a down-regulation of the Th17/Treg ratio. Furthermore, BBR indirectly modulated the Th17/Treg ratio by suppressing the secretion of TNF-α, IL-1ß, and IL-6 by DCs and enhancing the secretion of indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta (TGF-ß) by DCs. This dual action inhibited Th17 cell differentiation while promoting Treg cells. CONCLUSION: Our findings indicate that BBR regulate T cell subpopulation differentiation, reducing the Th17/Treg ratio by directly or indirectly pathway. This represents a potential therapeutic avenue of BBR for improving diabetic retinopathy.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding.

BACKGROUND: Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. RESULTS: This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. CONCLUSIONS: ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

The Association of Malnutrition and Health-Related Factors among 474,467 Older Community-Dwellers: A Population-Based Data Mining Study in Guangzhou, China.

BACKGROUND: This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors. METHODS: A total of 474,467 older community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition. RESULTS: The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity. CONCLUSIONS: Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.

New α-Glucosidase Inhibitors from the Whole Plant of Hypericum beanii Based on Ligand Fishing and Molecular Networking Analysis.

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.